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[6]-Gingerol Induces Cell Cycle Arrest and Cell Death of Mutant p53-expressing Pancreatic Cancer Cells

 Yon Jung Park  ;  Jing Wen  ;  Seungmin Bang  ;  Seung Woo Park  ;  Si Young Song 
 YONSEI MEDICAL JOURNAL, Vol.47(5) : 688-697, 2006 
Journal Title
Issue Date
Antineoplastic Agents/pharmacology* ; Antineoplastic Agents/therapeutic use ; Apoptosis/drug effects* ; Catechols ; Cell Cycle/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm ; Fatty Alcohols/pharmacology* ; Fatty Alcohols/therapeutic use ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mutation ; Pancreatic Neoplasms/drug therapy* ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Tumor Suppressor Protein p53/genetics* ; Tumor Suppressor Protein p53/metabolism
[6]-gingerol ; pancreatic cancer ; G1 phase ; apoptosis ; AKT
[6]-Gingerol, a major phenolic compound derived from ginger, has anti-bacterial, anti-inflammatory and anti-tumor activities. While several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo, the underlying mechanisms by which [6]-gingerol exerts anti-tumorigenic effects are largely unknown. The purpose of this study was to investigate the action of [6]-gingerol on two human pancreatic cancer cell lines, HPAC expressing wild-type (wt) p53 and BxPC-3 expressing mutated p53. We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression. These events led to reduction in Rb phosphorylation followed by blocking of S phase entry. p53 expression was decreased by [6]-gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21cip1, was p53-independent. [6]-Gingerol induced mostly apoptotic death in the mutant p53-expressing cells, while no signs of early apoptosis were detected in wild type p53-expressing cells and this was related to the increased phosphorylation of AKT. These results suggest that [6]-gingerol can circumvent the resistance of mutant p53-expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53-expressing cells by inducing temporal growth arrest.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Seung Woo(박승우) ORCID logo https://orcid.org/0000-0001-8230-964X
Bang, Seungmin(방승민) ORCID logo https://orcid.org/0000-0001-5209-8351
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
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